Initiation and progression of pulpal inflammation are due to alterations in the microcirculatory functions by humoral substances released during inflammation within the pulp. Thus, the specific aims of the project are to establish the roles of various humoral substances found in the pulp (catecholamine, prostaglandins substance P, vasoactive intestinal peptide, histamine and bradykinin) in affecting blood flow distribution, microvascular sites of action, permeability and tissue pressure using macrocirculatory and advanced microcirculatory methods. In macrocirculatory studies with dogs, pulpal blood flow will be determined using the Xe-133 washout and the radioisotope labeled 15 mum microsphere injection methods, pulpal tissue pressure will be determined using the servo-nulling micropipette technique and vascular permeability will be determined with the double isotope technique using I-131 and I-125 human serum albumin. In parallel microcirculatory studies with rat incisor teeth, vessel diameter, red cell velocity, flow and microvascular permeability will be measured by the intravital fluorescence microscope. Using these macro- and microcirculatory methods, effects of the humoral substance on the hemodynamic parameters will be investigated. Furthermore, an indepth investigation of prostaglandins and substance P, which are considered the key substances in pulpal inflammation, their mediating vascular actions, induced by other humoral substances, sympathetic and sensory nerve stimulation, will be conducted. Changes in pulpal tissue pressure, blood flow, permeability, and arterio-venous shunt flow in response to humoral substances will be analyzed to determine whether the extrapulpal perfusion pressure or the intrapulpal extravascular pressure is responsible for the control of pulpal hemodynamics. As a first step to investigate pulpal inflammation, vascular casts of experimentally induced inflamed pulps will be made and examined under a SEM. In addition, blood flow will be determined in the same pulp in order to study the structural-functional relationship in inflammation. The proposed investigations promise to attain the long-term objective of elucidating the humoral mechanisms in the regulation of pulpal hemodynamics and to shed light on the pathophysiological mechanisms of pulpal inflammation.